Asymmetric catalysis

ABSTRACT

Catalytic asymmetric hydrogenation of the Z geometric isomer of a compound of the formula ##STR1## wherein at least one of R and R 1  represents hydrogen and the other represents hydrogen, lower alkyl or aryl; R 2  represents ##STR2## wherein R 4  and R 5  each independently represent hydrogen, lower alkyl or aryl, R 6  represents hydrogen, lower alkyl, aryl or an alkali metal; and R 3  represents ##STR3## wherein R 7  and R 8  each independently represent lower alkyl or aryl; provided that, when R 3  is ##STR4## R 2  is --CN, in the presence of a homogeneous, coordination complex catalyst comprising rhodium, iridium or ruthenium in combination with an optically active bis phosphine ligand provides an outstanding level of optical purity.

This is a continuation of application Ser. No. 274,976 filed June 18,1981 abandoned which was a continuation-in-part of application Ser. No.854,447 filed Nov. 23, 1977 abandoned, which was a continuation ofapplication Ser. No. 607,304 filed Aug. 25, 1975 abandoned.

This invention relates to new catalytic asymmetric hydrogenationprocesses. More specifically, this invention is directed to ahydrogenation process which provides outstanding levels of opticalpurity.

Homogeneous catalysis, i.e., those catalyzed reactions that areconducted where both reactants and catalysts are soluble in the reactionmass, have been found to be particularly useful in processes wherein anasymmetric result is obtained. For instance, it has been found that whenan olefin, which is capable of forming a racemic mixture is hydrogenatedin the presence of a homogeneous, optically active catalyst, one or theother of the possible optical enantiomorphs is obtained in a majoramount with the other optical enantiomorph being obtained in minoramounts. Furthermore, it has been found that certain such olefinicsubstrates, for instance, precursors of α-amino acids containingα-acylamido and carboxylic acids, salts, esters or amides substituents,are particularly amenable to hydrogenation with homogeneous, opticallyactive catalysts. Such catalytic asymmetric hydrogenation processes haveresulted in the production of large amounts of the desired opticalenantiomorph. It has more recently been found that certain homogeneous,optically active catalysts containing optically active bis phosphineligands provide outstanding levels of optical purity, i.e., reaching 80%and higher with such α-amino acid precursors. Other olefinic substrateswhich would provide such outstanding levels of optical purity of opticalenantiomorphs leading to α-amino acids, upon hydrogenation, areparticularly desirable.

It is an object of the present invention to provide such olefinicsubstrates.

It is a further object to provide novel catalytic asymmetrichydrogenation processes which produce large amounts of the desiredoptical enantiomorph.

These and other objects, aspects and advantages of this invention willbecome apparent from a consideration of the accompanying specificationand claims.

SUMMARY OF THE INVENTION

In accordance with the above objects, the present invention providescatalytic asymmetric hydrogenation of the Z geometric isomer of acompound of the formula ##STR5## wherein at least one of R and R¹represents hydrogen and the other represents hydrogen, lower alkyl oraryl; R² represents ##STR6## wherein R⁴ and R⁵ each independentlyrepresent hydrogen, lower alkyl or aryl, R⁶ represents hydrogen, loweralkyl, aryl or an alkali metal; and R³ represents ##STR7## wherein R⁷and R⁸ each independently represent lower alkyl or aryl; provided that,when R³ is ##STR8## R² is --CN, in the presence of a homogeneous,coordination complex catalyst comprising rhodium, iridium or rutheniumin combination with an optically active bis phosphine ligand. Thisprocess provides outstanding levels of optical purity of desired opticalenantiomorphs.

DESCRIPTION OF THE PREFERRED EMBODIMENTS

The hydrogenation reaction is illustrated by the following equation:##STR9##

It has been found that the geometric stereochemistry of the olefinicsubstrate being hydrogenated effects the results obtained. In general,it is necessary to utilize the Z geometric isomer to realize theoutstanding levels of optical purity with the olefinic substrates ofthis invention. The E and Z geometric isomer nomenclature is describedin detail in The Journal of Organic Chemistry, Vol. 35, No. 9, September1970, pp 2849-2867. It has been found that either the E or Z geometricisomer will, upon hydrogenation, produce the same optical enantiomorphwhen using the same catalyst but at different levels of optical purity.

R, R¹, R⁴ and R⁵ are each independently exemplified by hydrogen, loweralkyl groups (e.g. methyl, ethyl, propyl, butyl, amyl) and by arylgroups such as phenyl. The alkyl and phenyl groups may be unsubstitutedor they may be substituted by a large number of groups and suchsubstituents are limited only by the desired make-up of the opticalenantiomorph that is the desired end-product. Exemplary substituentgroups may include methyl, ethyl, methoxy and acetoxy.

R⁶ is exemplified by hydrogen, lower alkyl, aryl as described above oralkali metal groups such as sodium, potassium or lithium.

R⁷ and R⁸ are independently exemplified by lower alkyl or aryl groups asdescribed above.

As described above, the alkyl or aryl groups may be substituted by alarge variety of groups. Further, it may be that such substituent groupsmay be precursors of desired substituents. Thus, if the desiredsubstituent on the saturated end-product is hydroxyl, the substituent onthe unsaturated substrate might be ##STR10## which would provide thehydroxyl group by simple hydrolysis after the catalytic asymmetrichydrogenation.

The optical enantiomorphs resulting from the process of this inventionare particularly desirable in that optical activity is a desirablecharacteristic of α-amino acids, i.e. normally only one or the otheroptical enantiomorphs is useful in living organisms. For instance, thoseoptical enantiomorphs of α-amino acids resulting from this process whichhave phenyl or substituted phenyl substituents on the β position lead todesirable L-phenylalanines.

The compounds represented by the following structural formula provideexcellent results with the process of this invention and thereforerepresent compounds particularly amenable to the hydrogenation processof this invention ##STR11## wherein R and R¹ have the same meaning asdescribed above.

Particularly preferred embodiments of this invention are the catalyticasymmetric hydrogenation of(Z)-ethyl-2-(N-ethoxycarbonylamino)-3-phenyl-2-propenoate (Compound I,below. Note, also, Example 1) and(Z)-2-benzamido-3-phenyl-2-propenenitrile (Compound II, below. Note,also, Example 4). ##STR12##

The L enantiomorph of phenylalanine can be readily derived from suchprocedures.

Such hydrogenation reactions are usually conducted in a solvent, such asbenzene, ethanol, 2-propanol, toluene, cyclohexane, and mixtures ofthese solvents. Almost any aromatic or saturated alkane or cycloalkanesolvent, which is inactive to the hydrogenation conditions of thisreaction, can be used. The preferred solvents are alcohols particularlymethanol, ethanol and 2-propanol.

The homogeneous, optically active catalysts useful in this invention aresoluble coordination complexes comprising a metal which is rhodium,iridium or ruthenium in combination with at least one optically activebis phosphine ligand, preferably at least about 0.5 moles of bisphosphine ligand per mole of metal. These catalysts are soluble in thereaction mass and are therefore referred to as "homogeneous" catalysts.

These catalysts contain optically active bis phosphine compounds ofgeneral formulae I and II below. These bis phosphine compounds arecharacterized by the structural formula ##STR13## wherein A and B eachindependently represent substituted and unsubstituted alkyl of from 1 to12 carbon atoms, substituted and unsubstituted cycloalkyl having from 4to 7 carbon atoms, substituted and unsubstituted aryl; provided thatsuch substituents provide no significant interference with the stericrequirements around the phosphorus atom and A and B are different.

Among such bis phosphine compounds, those having two dissimilar arylgroups on each phosphorus atom are also preferred, particularly thosewherein one such aryl group has an alkoxy substituent at the orthoposition.

More preferred bis phosphine compounds useful in the present inventionare the optically active bis phosphines characterized by the structuralformula ##STR14## wherein

X represents substituted and unsubstituted phenyl,

Y represents substituted and unsubstituted 2-alkoxyphenyl wherein thealkoxy has from 1 to 6 carbon atoms; provided that such substituentsprovide no significant interference with the steric requirements aroundthe phosphorus atom and X and Y are different.

The catalysts prepared utilizing those optically active bis phosphinecompounds of more specific formula III, below, are more particularlypreferred in the catalytic asymmetric hydrogenation reactions of thisinvention.

Still more particularly preferred optically active bis phosphinecompounds useful in the present invention are characterized by thestructural formula ##STR15## wherein M represents ##STR16## N represents##STR17## R' and R" each independently represent hydrogen, halogen,alkyl having from 1 to 6 carbon atoms and alkoxy having from 1 to 6carbon atoms, and

R'" represents normal alkyl having from 1 to 6 carbon atoms;

provided that M and N are different.

A particularly preferred optically active bis phosphine compound usefulin the present invention is 1,2-bis(o-anisylphenylphosphino) ethane.

Other exemplary optically active bis phosphine compounds useful in thisinvention are:

1,2-bis(o-anisyl-4-methylphenylphosphino) ethane

1,2-bis(o-anisyl-4-chlorophenylphosphino) ethane

1,2-bis(o-anisyl-3-chlorophenylphosphino) ethane

1,2-bis(o-anisyl-4-bromophenylphosphino) ethane

1,2-bis[(2-methoxy-5-chlorophenyl)-phenylphosphino] ethane

1,2-bis[(2-methoxy-5-bromophenyl)-phenylphosphino] ethane

1,2-bis(2-ethoxyphenylphenylphosphino) ethane

1,2-bis[o-anisyl-(p-phenylphenyl)phosphino] ethane

1,2-bis[(2-methoxy-4-methylphenyl)-phenylphosphino] ethane

1,2-bis(2-ethoxyphenyl-4-chlorophenylphosphino) ethane

1,2-bis(o-anisyl-2-methylphenylphosphino) ethane

1,2-bis(o-anisyl-4-ethylphenylphosphino) ethane

1,2-bis(o-anisyl-3-ethylphenylphosphino) ethane

1,2-bis(o-anisyl-3-phenylphenylphosphino) ethane

For these bis phosphine compounds to be useful in asymmetrichydrogenation reactions they must be utilized as the optically activeenantiomorph and not in the meso form.

Optically activity of the coordinated complex catalysts useful in thisinvention resides in the bis phosphine ligand. This optical activityresults from having two different groups, in addition to the ethanebridge, on the phosphorus atom.

Illustrative coordination metal complexes can be represented by theformula MeTL wherein Me is a transition metal selected from the groupconsisting of rhodium, iridium and ruthenium; T is selected from thegroup consisting of hydrogen, fluorine, bromine, chlorine and iodine; Lis the optically active bis phosphine ligand as previously defined.

It has been found that outstanding levels of optical purity of thedesired optical enantiomorphs can be achieved not only with theabove-described catalysts represented by the formula MeTL, which arecoordination complexes of a metal selected from the group consisting ofrhodium, iridium and ruthenium, but can also be achieved when thehydrogenation is carried out in the presence of an in situ complexcatalyst that comprises a solution of a transition metal selected fromthe group consisting of rhodium, iridium and ruthenium and at leastabout 0.5 moles of the optically active bis phosphine ligand per mole ofmetal. For instance, such catalysts can be prepared by dissolving asoluble compound of the appropriate metal in a suitable solvent togetherwith an optically active bis phosphine compound as the ligand whereinthe ratio of ligand to metal is at least 0.5 moles of ligand per mole ofmetal, preferably one mole of ligand per mole of metal. It has beenfound that the catalyst is formed in situ by adding a soluble metalcompound to the reaction mass together with the addition of the properamount of the optically active bis phosphine ligand to the reaction masseither before or during hydrogenation.

The preferred metal for use in this process is rhodium. Soluble rhodiumcompounds that can be utilized include rhodium trichloride hydrate,rhodium tribromide hydrate, rhodium sulfate, organic rhodium complexeswith ethylene, propylene, etc., and bis olefins such a1,5-cyclooctadiene and 1,5-hexadiene, bicyclo-2.2.1-hepta-2,5-diene andother dienes which can form bidentate ligands, or an active form ofmetallic rhodium that is readily solubilized.

It has been found that a preferred embodiment of this invention is thehydrogenation process where the optically active bis phosphine ligand ispresent in a ratio of about 0.5 to about 2.0, preferably, 1.0, moles ofbis phosphine ligand per mole of metal. In practice, it is preferred tohave the optically active catalyst in a solid form for purposes ofhandling and storage. It has been found that outstanding results can beobtained with solid, cationic coordination metal complexes.

Cationic coordination metal complexes containing one mole of theoptically active bis phosphine ligand per mole of metal and a chelatingbis olefin represent a preferred form of the catalysts useful in thepresent invention. For instance, using organic rhodium complexes, asdescribed above, one can prepare such cationic coordination rhodiumcomplexes by slurrying the organic rhodium complex in an alcohol, suchas ethanol, adding one mole per mole of rhodium of the optically activebis phosphine compound so that an ionic solution is formed, followed bythe addition of a suitable anion, such as, for instance,tetrafluoroborate, tetraphenylborate or any other anion that will resultin the precipitation or crystallization of a solid, cationiccoordination metal complex either directly from the solvent or upontreatment in an appropriate solvent.

Exemplary cationic coordination metal complexes arecyclooctadiene-1,5-[1,2-bis(o-anisylphenylphosphino) ethane] rhodiumtetrafluoroborate, cyclooctadiene-1,5-[1,2-bis(o-anisylphenylphosphino)ethane] rhodium tetraphenylborate andbicyclo-2.2.1-hepta-2,5-diene-[1,2-bis(o-anisylphenylphosphino) ethane]rhodium tetrafluoroborate.

Without prejudice to the present invention it is thought that thecatalyst is present actually as a catalyst precursor and that uponcontact with hydrogen the catalyst is converted to an active form. Thisconversion can, of course be carried out during the actual hydrogenationor can be accomplished by subjecting the catalyst (or precursor) tohydrogen prior to addition to the reaction mass to be hydrogenated.

As previously noted, the catalyst can be added to the solvent either asa compound per se or as its components which then form the catalyst insitu. When the catalyst is added as its components it may be added priorto or after the addition of the olefinic substrate. Components for thepreparation of the catalyst in situ are the soluble metal compound andthe optically active bis phosphine compound. The catalyst can be addedin any effective catalytic amount and generally in the range of about0.001% to about 5% by weight of contained metal based on the olefinicsubstrate to be hydrogenated.

Within the practical limits, means should be provided so as to avoidcontacting the catalyst or reaction mass with oxidizing materials. Inparticular, care should be taken so as to avoid contact with oxygen. Itis preferred to carry out the hydrogenation reaction preparation andactual reaction in gases (other than H₂) that are inert to bothreactants and catalysts such as, for instance, nitrogen or argon.

After addition of the reactants and catalyst to the solvent, hydrogen isadded to the mixture until about 0.5 to about 5 times the mole quantityof the olefinic substrate present has been added. The pressure of thesystem will necessarily vary since it will be dependent upon the type ofreactant, type of catalyst, size of hydrogenation apparatus, amount ofreactants and catalyst and amount of solvent. Lower pressures, includingatmospheric and sub-atmospheric pressure can be used as well as higherpressure.

Reaction temperatures may be in the range of about -20° C. to about 110°C. Higher temperatures may be used but are normally not required and maylead to an increase of side reactions.

Upon completion of the reaction which, is determined by conventionalmeans, the product is recovered by conventional means.

Many naturally occurring products and medicaments exist in an opticallyactive form. In these cases only the L or D form is usually effective.Synthetic preparation of these compounds in the past has required anadditional step of separating the products into its enantiomorphs. Thisprocess is expensive and time consuming. This process of the presentinvention permits the direct formation of desired optical enantiomorphswith outstanding optical purity thus eliminating much of the timeconsuming and expensive separation of such optical enantiomorphs.Furthermore, the process provides a higher yield of the desired opticalenantiomorph while concurrently decreasing the yield of the unwantedoptical enantiomorph.

The hydrogenation process of this invention is particularly desirablebecause of its ability to not only provide an unusually high opticalpurity of the desired optical enantiomorph but also because of itsability to afford a rapid rate of hydrogenation at low catalystconcentrations.

The following examples will serve to illustrate certain specificembodiments within the scope of this invention and are not to beconstrued as limiting the scope thereof. In the examples, the percentoptical purity is determined by the following equation (it beingunderstood that the optical activity, expressed as specific rotation, ismeasured in the same solvent): ##EQU1##

EXAMPLE 1 Preparation of(Z)-ethyl-2-(N-ethoxycarbonylamino)-3-phenyl-2-propenoate

To a solution of 21.0 g. (0.12 mole) of ethyl N-(ethoxycarbonyl)glycine, 10.08 g. (0.096 mole) of benzaldehyde and 200 ml. of ethyleither, maintained at 5° C., was added 3.0 g. (0.13 mole) of sodiummetal. The mixture was stirred 18 hours at ambient temperature and wasfiltered to remove the solid precipitate. The ethereal filtrate waswashed with water and dried. The ether was stripped and the solidresidue was recrystallized from toluene. The yield was 4.9 g., m.p.102-107. The product was identified as(Z)-ethyl-2-(N-ethoxycarbonylamino)-3-phenyl-2-propenoate by NMR, GLC,and UV analysis.

EXAMPLE 2 Preparation ofethyl-2-(N-ethoxycarbonylamino)-3-phenylpropanoate

A solution 2.29 g. of(Z)-ethyl-2-(N-ethoxycarbonylamino)-3-phenyl-2-propenoate, 0.0105 g. ofcyclooctadiene-1,5-[1,2-bis(o-anisylphenylphosphino) ethane] rhodiumtetrafluoroborate and 30 cc. of ethanol was hydrogenated at 3 atm. and50° C. After 21/2 hours, the solution was stripped on a rotaryevaporator. NMR analysis indicated that hydrogenation was complete.

The hydrogenation product,ethyl-2-(N-ethoxycarbonylamino)-3-phenylpropanoate, was hydrolyzed tophenylalanine (with the L enantiomorph in major amount) in the followingmanner: To a solution of the residue from the above stripping in 30 cc.of acetic acid at 75° C., hydrogen bromide gas was slowly bubbled in theresulting solution for 1 hour. After holding for several hours, theacetic acid was removed on a rotary evaporator. The resulting residuewas added to 25 cc. of water containing 2 cc. of 48% aqueous hydrogenbromide. The mixture was heated at reflux for 31/2 hours, cooled to 25°C. and extracted with chloroform to remove non-hydrolyzed organics. Thewater solution, containing the phenylalanine hydrobromide salt and 1 cc.of added acetic acid was neutralized to pH 3 with a 50% NaOH solution.The optical rotation of the neutralized solution (100 cc.), containingthe phenylalanine was determined with a polarimeter. [α]_(D) ²⁰ =-27.95°(C=1 in water), optical purity equals 88.7%.

EXAMPLE 3 Preparation of N-benzamidoacetonitrile

Sodium carbonate (0.108 mole) was added to a solution containing 20 g.of aminoacetonitrile hydrochloride (0.216 mole) in 150 cc. of water. Thesolution was cooled to 5° C. and 18.1 g. (0.216 mole) of sodiumbicarbonate was added. 30.4 g. of benzoyl chloride (0.216 mole) wasadded dropwise over about 11/2 hours to the cold aqueous solution and asolid formed. The resulting mass was allowed to warm to 20° C.; thesolid was collected and washed thoroughly with water. The dry weight ofthe recovered material, which was crude N-benzamidoacetonitrile, was 33g. (96% yield) m.p. 137°-139° C. This material was recrystallized from100 cc. of methanol and 29 g. was recovered.

EXAMPLE 4 Preparation of (Z)-2-benzamido-3-phenyl-2-propenenitrile

Hydrogen chloride gas was bubbled into a solution containing 4 g. ofbenzaldehyde (0.037 mole) and 6 g. of N-benzamidoacetonitrile (0.037mole) in 100 cc. of diethyl ether maintained at 0°-5° C. Upon holdingfor about 11/2 hours a solid precipitates 10.4 g. of this solid wascollected by filtration.

The 10.4 g. of the solid collected above was added to a solution of 4 g.of sodium carbonate in 100 cc. of cold (0°-5° C.) water. The mixture wasstirred for 1 hour at 5° C., then 10 cc. of acetone was added and theresulting mass allowed to warm to 20° C. The product, which was crude(Z)-2-benzamido-3-phenyl-2-propenenitrile (NMR), was collected andwashed with water. The dry weight of collected material was 8.5 g. (92%yield). The 8.5 g. of this material was crystallized from 85 cc. ofethanol. Recovery was 6.8 g., m.p. 164°-165°.

EXAMPLE 5 Preparation of 2-benzamido-3-phenylpropanenitrile

(A) A solution of 0.9956 g. of(Z)-2-benzamido-3-phenyl-2-propenenitrile, 0.0046 g. ofcyclooctadiene-1,5-[1,2-bis(o-anisylphenylphosphino) ethane] rhodiumtetrafluoroborate and 0.5 cc. of acetic acid in 30 cc. of methanol washydrogenated in a Hoke bomb at 27 atm. and 50° C. Hydrogenation wascomplete in 3 hours. The solution was diluted to 200 cc. with methanol,observed rotation=-0.359°, [α]_(D) ²⁰ =-72.1°. The pure enantiomorph of2-benzamido-3-phenylpropanenitrile in a solution of comparablecomposition has a [α]_(D) ²⁰ =-84.3°. Therefore, the optical purity was85.5%.

(B) A solution of 0.9924 g. of(Z)-2-benzamido-3-phenyl-2-propenenitrile, 0.0153 g. ofcyclooctadiene-1,5-[1,2-bis(o-anisylphenylphosphino) ethane] rhodiumtetrafluoroborate and 2 drops of acetic acid in 30 cc. of methanol wassubjected to 3 atm. of hydrogen pressure at 50° C. After about 24 hours,the solution was diluted to 200 cc. with methanol. The observed rotationwas -0.372°,[α]_(D) ²⁰ =-75°. Therefore, the optical purity was 89%.

While the invention has been described herein with regard to certainspecific embodiments, it is not so limited. It is to be understood thatvariations and modifications thereof may be made by those skilled in theart without departing from the spirit and scope of the invention.

The embodiments of this invention in which a particular property orprivilege is claimed are defined as follows:
 1. An asymmetrichydrogenation process comprising hydrogenating an olefinic substrateconsisting essentially of the Z geometric isomer of a compound of theformula ##STR18## wherein at least one of R and R¹ represents hydrogenand the other independently represents hydrogen, unsubstituted orsubstituted lower alkyl or aryl; R² represents ##STR19## wherein R⁴ andR⁵ each independently represent hydrogen, unsubstituted or substitutedlower alkyl or unsubstituted or substituted aryl, R⁶ representshydrogen, unsubstituted or substituted lower alkyl or unsubstituted orsubstituted aryl; and R³ represents ##STR20## wherein R⁷ and R⁸ eachindependently represent unsubstituted or substituted lower alkyl orunsubstituted or substituted aryl; provided that when R³ represents##STR21## R² represents --CN, in the presence of a catalytic amount of ahomogeneous, coodination complex of rhodium, iridium or ruthenium incombination with an optically active bis phosphine ligand represented bythe formula ##STR22## wherein A and B each independently representsubstituted and unsubstituted alkyl of from 1 to 12 carbon atoms,substituted and unsubstituted cycloalkyl having from 4 to 7 carbonatoms, substituted and unsubstituted aryl; provided that suchsubstituents provide no significant interference with the stericrequirements around the phosphorus atom and A and B are different.
 2. Ahydrogenation process according to claim 1 wherein the bis phosphineligand is represented by the formula ##STR23## wherein X representssubstituted and unsubstituted phenyl,Y represents substituted andunsubstituted 2-alkoxyphenyl wherein the alkoxy has from 1 to 6 carbonatoms; provided that such substituents provide no significantinterference with the steric requirements around the phosphorus atom andX and Y are different.
 3. A hydrogenation process according to claim 1wherein the bis phosphine ligand is represented by the formula ##STR24##wherein M represents ##STR25## N represents ##STR26## R' and R" eachindependently represent hydrogen, halogen, alkyl having from 1 to 6carbon atoms and alkoxy having from 1 to 6 carbon atoms, andR'"represents normal alkyl having from 1 to 6 carbon atoms;provided that Mand N are different.
 4. A hydrogenation process according to claim 1wherein the bis phosphine ligand is 1,2-bis(o-anisylpenylphosphino)ethane.
 5. A process according to claim 1 wherein the metal utilized inthe catalyst complex is rhodium.
 6. A process according to claim 2wherein the metal utilized in the catalyst complex is rhodium.
 7. Aprocess according to claim 3 wherein the metal utilized in the catalystcomplex is rhodium.
 8. A process according to claim 4 wherein the metalutilized in the catalyst complex is rhodium.
 9. A hydrogenation processaccording to claim 1 wherein the compound being hydrogenated isrepresented by the formula ##STR27##
 10. A hydrogenation processaccording to claim 2 wherein the compound being hydrogenated isrepresented by the formula ##STR28##
 11. A hydrogenation processaccording to claim 3 wherein the compound being hydrogenated isrepresented by the formula ##STR29##
 12. A hydrogenation processaccording to claim 4 wherein the compound being hydrogenated isrepresented by the formula ##STR30##
 13. A hydrogenation processaccording to claim 5 wherein the compound being hydrogenated isrepresented by the formula ##STR31##
 14. A hydrogenation processaccording to claim 1 wherein the compound being hydrogenated is(Z)-2-benzamido-3-phenyl-2-propenenitrile.
 15. A hydrogenation processaccording to claim 1 wherein the compound being hydrogenated is##STR32##
 16. A hydrogenation process according to claim 2 wherein thecompound being hydrogenated is ##STR33##
 17. A hydrogenation processaccording to claim 3 wherein the compound being hydrogenated is##STR34##
 18. a hydrogenation process according to claim 4 wherein thecompound being hydrogenated is ##STR35##
 19. A hydrogenation processaccording to claim 5 wherein the compound being hydrogenated is##STR36##
 20. A hydrogenation process according to claim 1 wherein thecompound being hydrogenated is(Z)-ethyl-2-ethyl-2-(N-ethoxycarbonylamino)-3-phenyl-2-propenoate.